Samsung Galaxy Tab simfree: Very low price range

Mobile phones have always been considered as the most useful gadgets. These have not only provided the solutions for the voice communication features but have offered many other advantages as well. The modern era gadgets offer much more than the simple communication. The gadgets have started to be known for the various other factors as well.

The new specialities of the mobile phones can be best checked out with the Samsung Galaxy Tab. The mobile phone holds the beauty in both the aspects – internal and external as well. The mobile phone is superior in looks along with the mind blowing range of features. The wide 7.0 inches touchscreen of the handset will make you enjoy the incredible features. The handset is a very classical combination of looks and mind blowing features. Internet facility can also be best enjoyed on the mobile as the handset incorporates that features like the GPRS, EDGE, WLAN, etc. The mobile phone works on the operating system of Android version 2.2 (Froyo). Moreover it also holds the PowerVR SGX540 graphics. The mobile is coming in two variants that are 16 GB and 32 GB respectively.

Along with it, the mobile also offers the Full HD video playback. The deals for the mobile phone are also available in oodles of formats like the contract deals and pay as you go deals formats. But the best way to achieve the mobile phone is through the sim free deals. The deals are available with almost all the networks but the best deals are coming with the tag name Samsung Galaxy Tab Orange deals. The sim free phones deals for the handset are offering the mobile for just £ 632.7. The best way to get the view of the deals is through internet. Many online price comparing web sites are comparing the deals for the mobile to make you get the cheapest of deals. This will also facilitate you in cracking the deals with the most numbers of benefits.


Source by: Tomy Nastey


Fantastic Apple peel 520 – Change iPod Touch to iPhone in a Moment

Apple peel 520 is a product that supposedly gives the iPod touch cellular functions. Since the iPod touch and the iPhone are very similar in dimensions and in software, there is a great possibility this can be used for the iPhone.

However, this fantastic assemble has its own advantages and disadvantages. I’d love to be able to seek some more value out of my 1st Gen iPod Touch if it were possible… Still this is the first and the only apple device I own, and i still won’t upgrade till it’s broke for good. Another and which also the biggest advantage is it can save you a lot of money for those who love iphone so much but are terrified by the sight of price. Ipod touch usually starts at 229, and the apple peel 520 sold at PickEgg.com only $109 …it maybe the lowest price all over the world and no need to pay deliver charge.

If you want to see the fantastic creation, you need to buy it immediately and I think there would not be a day when it was $60. You may as well get lucky on PickEgg for an apple peel 520 at that point.

Maybe the greatest reason for this even exists is because the designer either couldnt afford an iphone or did not want to pay as much. Getting a much cheaper touch and adding this device he created, gave him the functionality of the iphone at a lower cost. At last i heard he was trying to find out if his product was legal.

The difference is this way you can actually make calls” is what I would’ve said if I was an uneducated jackass.

There are also disadvantages: the iPod with the Peel currently has a problem with the “death grip” and in general, it wasn’t engineered optimally for calling. If this product works as advertised, then you can use this instead of a bumper to get rid of the “death grip” problem and at the same time possibly improve the reception on your ipod. For new people and if you have enough money, choosing between the iPod touch + this vs the iPhone 4, I would recommend the iPhone 4 since it is not dependent on an accessory whose functionality seems pretty shady to me. But to somebody else, it like it’s targeting preteens etc who already have an iPT instead of getting a new phone.

Another problem I see is there is no earpiece. Are all calls going to go over speakerphone or Bluetooth? No like a good idea, but I need an earpiece. That’s one reason I’m not getting a Samsung Galaxy Tab. Yeah sure, I might look like a who knows what with a 7 inch “Tab” next to my head but I don’t care. I hate BT headsets and I can’t have people hearing my conversations. I hardly make calls as it is but when I do I need an earpiece. So close too.

In generally, to most of the people who know this device, still sticking it to Apple. Now you don’t have to buy the wallet-dissolving iPhone.

Also, to most of the people, who know Apple Peel 520 and take quick visit to the website with this product for sale. And this did nothing to allay our lingering suspicions — in through and through-it appeared to be hastily-cobbled cash– but still, sorely tempted our wallet for the prospect of an iPod touch case with cellular capabilities. The Peel520.net may give you siren call to advise you attempting a purchase, but after make serious cooperation. Also the Google tells us their owners of the apple peel 520 are one and the same with PickEgg, so if you bought one of those sim-cutting devices and got your product as promised, PickEgg suppose you’re liable to get a better deal. But if you have qualms, well — wait for Go Solar to formally bring the product to market, or else steer clear.


Source by: hebe

How to convert TOD to mobile phone 3GP/3G2/3GPP/3GPP2?

TOD to Mobile Phone converter easily converts JVC TOD video files 3GP/3G2/3GPP/3GPP2 for importing into various cell phones Samsung Propel/Nokia N95/Motorola V8

TOD to Mobile Phone converter is a great converting JVC Everio TOD video file to Mobile phones 3GP for putting into Samsung Propel and Nokia N95. It empowers you to convert TOD to MOV for QuickTime, convert TOD to MP4 for iPod/iPhone/PSP, convert JVC TOD to AVI for importing to Xbox/iRiver, convert TOD to WMV for putting into Windows Movie Maker and convert JVC Everio TOD to DV for editing with Final Cut Pro.

                        Any interest, free to download here for evaluation!

Windows 7 program converting tool TOD to Mobile Phone 3GP converter accept to inputted, MOD, Matroska MKV, QuickTime MOV, DVD files VOB and Moving Export Group MPEG, converting FLV to 3GP, MOV to 3G2, MOD to 3GP, MPG to 3GP putting into mobile phone. You can only extract audio from video files and save them as AAC, AC3, AIFF, AMR, FLAC, M4A, MKA, MP3, MP2, RA, WAV, WMA for listening with cell phone.

How to put TOD video files recorded by JVC Everio on Samsung Propel SGH-A767 and play video files on Nokia 5310/5300/6133/N75/N95?

1.How can I play my video/movie clips onto my newly Samsung Propel A767? What video files are supported on a Propel? I am wondering if anyone has had any success converting movies so they can be watched on the Propel.
2.The video and audio do not match on Nokia 5300, how to convert to the proper format and put it right?

Cell phones are more than just convenient communication tools: They allow you to check e-mail, sync with the calendar and contacts on your PC, dial a number by the sound of your voice, surf your favorite Web sites, take photos, play games, send text messages, view and edit documents, listen to music, and more. Samsung and Nokia phone have gradually gained their popularity in the world. However, putting video files into Samsung Propel/Galaxy/Nokia 5300/Motorola V8 for playing is impossible due to format unsupported.

TOD to Mobile Phone converter has the ability to solve your headache by converting TOD video files to Mobile phone compatible formats. Four preset aspect ratio allows you to define your preferred visual size, Original, Full Screen, 4:3, 16:9; preset advanced video setting helps you to select video Encode, Resolution, Bit rate, Frame rate to fit for your differed screen size of your mobile phone.

You are free to use TOD to Mobile Phone converter to tweak video Saturation, contrast, Brightness to get a better visual effect on mobile phone. This converting program is total clean without attaching any virus and adware.

Key feature of transferring TOD to 3GP/3G2 for importing into Mobile Phone

1. Input video formats
TOD, MOD, MKV, MPG, MP4, MOV, VOB

2. Output video formats
SWF, FLV, AVI, MKV, MOV, MP4, WMV, MMPG, 3GP, DV, RM, RMVB

3. Output audio formats
MP3, FLAC, AAC, AC3, WMA, MKA, AMR,M4A, MP2

4. Take snapshot
Capture favored images in JPG, BMP and PNG format

5. Rotate video
Flip video upside down and left to right for fun

6. Crop
Cut off black edges and unwanted subtitle

7. Trim
Set the range of video to be converted

8. Add effects
Add artistic effects like Emboss, Old Film and Gray

Step by step tutorial for teaching you to convert TOD to Mobile Phone on Windows 7/Vista

Step one: download TOD to Mobile Phone converter and install
Step two: run converter and load TOD files
Step three: set output formats and destination
Step four: crop, trim and add effects
Step five: start JVC TOD to Mobile Phone conversion

TOD to Mobile Phone Converter


Source by: jolly

Samsung Galaxy S Deals: Buy latest samsung galaxy s mobile phones

The brand has a long list of successful handsets that have Samsung a reliable brand. Samsung Galaxy S is the latest handset launched by the brand ,this handset comes loaded with latest features that will definitely make you go crazy. User can get this handset with various Samsung Galaxy S Contract on many sites.There are many features in this handset that are just outstanding,firstly the display of the handset is jaw dropping as it ha a 4.0 inches Super AMOLED capacitive touchscreen that supports 16M colors and also features TouchWiz 3.0 UI, Multi-touch input method, Accelerometer sensor for UI auto-rotate, Touch-sensitive controls, Proximity sensor for auto turn-off and Swype text input that make the looks of the handset very attractive.

Secondly the Samsung Galaxy S Deals comes with a whooping internal memory of 8GB and also ha an external memory slot that supports a memory card of up to a memory space of 32GB that gives user a huge space to store his data and files. One of the most amazing feature is the integreted 5MP camera with 720p@30fps video capability,autofocus and features like Geo-tagging, touch focus, face and smile detection that makes it equivalent to a digital camera. It also has a secondary camera for video calling option. Android OS, v2.1 (Eclair) is the working platform for the handset and it ha a ARM Cortex A8 1GHz powerful processor.

The HTML browser gives problem free internet access and messaging facilities like SMS(threaded view), MMS, Email, Push Mail, IM, RSS keeps you connected with your loved ones and keeps you updated with the latest happenings that take place around the world. The user gets this mobile phones in Black and Grey colors.The customer can this handset through many network companies like O2,Orange,Vodafone,Virgin etc. they give Samsung Galaxy S contract.These deals include lucrative offers that gives free gifts and incentives that help in reducing monthly phone bills so you get to save your hard earned money.


Source by: Day Kevi

Review the Latest Tablet PC and Compare Tablet Computer


A tablet personal computer (tablet PC) is a portable personal computer equipped with a touch screen as a primary input device. Comparing laptops, tablet personal computers may not be equipped with a keyboard, in which case they use a virtual onscreen substitute. All tablet personal computers have a wireless adapter for Internet and local network connection. The term was made popular as a concept presented by Microsoft in 2001, yet the Tablet computer market was invigorated by Apple through the introduction of the iPad device in 2010. Apple’s iPad, are readying their own devices for what is already proving to be a rapidly growing marketplace. According to Apple, the company shipped “4.19 million iPads during the quarter.” During the Q3 earnings call, in the first full quarter in which the iPad was available, that number stood at just over 3 million. The iPad only weighs 1.5lbs, gives you a display of 9.56 in (24.3 cm) × 7.47 in (19.0 cm) and is only 0.5 inches thick. The battery Life of iPad is up to 10 hours. These dimensions couldn’t be any handier and puts the iPad in a class of its own. iPad use of the iPhone OS and its clever data-entry scheme – virtual keyboard, multitouch gestures and all – turns the iPad into an immeasurably more usable device than any Windows-based tablet PC we’ve seen. In general, the iPad it’s not a Netbook killer, but it will take away revenues from that market. Meanwhile, Dell Streak tablet device, perhaps is basically just a smartphone. Its five-inch touchscreen puts it somewhere in between an iPhone (screen size: 3.5 inches) and an iPad (9.7 inches). The Streak’s operating system is limited. Like many current and future iPad competitors, it uses Google’s Android OS. In this case, however, the Streak is using an older version of Android, version 1.6. The latest version of Android is Android 2.2 (also known as “Froyo”), so Streak gets a late pass.

Then, Samsung is readying its new tablet, the Galaxy. It is a true tablet, with a touchscreen that measures 7 inches diagonally. When it is released in late October or early November, it too will be sold through mobile carriers — all four big ones (AT&T, Sprint, T-Mobile and Verizon), in fact. The Galaxy will run on Android version 2.2.
Many of the apps available in the Android Market, when scaled to fit on the Galaxy’s comparatively gargantuan 7-inch display, are not going to look all that pretty, if they look like anything at all.There is another Android upgrade in the works (Android 3.0, a.k.a. “Gingerbread”), which may play more nicely with tablets like the Galaxy.

HP is coming a webOS-based tablet unofficially dubbed the PalmPad for release early next year. Things get very muddled, however, when the talk turns to HP’s Android tablet and Windows tablet PC plans.

For starters, design is less a factor for tablets than in the other categories. A tablet is supposed to be a mostly featureless panel of glass: that is the whole point. The hardware will also be fairly standardized (display, cameras, microphone, chipset). The only question will be who has the most and best apps.And if that is the key (and it is), then consumers are not actually the people that tablet makers should be concerned about right now — it is the app developers. Win them over, and the shoppers will follow.


Source by: timili

Top Ten Most Expensive Exotic Cars

Exotic cars are high end sports cars whose performance is superior to that of its contemporaries. They are typically very expensive and powerful cars that designed with a centrally located engine. Exotic cars are always very sleek and catch the eyes of people wherever they are. The prices of these types of cars are almost always in a class of their own and are only attainable by the most elite and wealthy people in the world. Below is a list of the top ten most expensive exotic cars in the world.

1. Mercedes Benz SLR. This luxury car is a German sports car that was jointly developed by Mercedes Benz and McLaren Automotive. It is the fastest automatic transmission car in the world and is priced at nearly $450,000.

2. Porsche Carrera GT. This is a mid engined sports car and was voted the fastest car of the year in 2005. The price tag of this car is $440,000.

3. Saleem S7. If you want to call this car your own you will need to be willing to cough up a cool $430,000.

4. Maybach 62. This is a full size luxury car that was introduced in 2002. The price tag if you want to take this car home is $357,000.

5. Rolls Royce Phantom. This is a British luxury saloon automobile manufactured by Rolls Royce Motor Cars in the United Kingdom. Rolls Royce launched this luxury automobile in 2003 and it is currently priced at $320,000.

6. Maybach 57. This exotic car that was introduced to the public in 2005 at the Geneva Motor Show. This automobile has a price tag of $305,500.

7. Lamborghini Murcielago. This is an Italian sports car that was introduced to the market in 2002. It is a six speed engine two door coupe model. If you want to house this car in your garage you will have to pay a sum of $279,900.

8. Ferrari 612. The Ferrari 612 is an exotic car in the Gran Turismo class. It was introduced to the public in 2004 as a two door coupe with a six speed manual engine. Today, this car is priced at $259,855.

9. Bentley Arnage. This is a luxury car produced in England by Bentley Motors. The production of this vehicle began in 1998 and is still active today. The price of this luxury car is $250,000.

10. Aston Martin V12 Vanquish. This luxury car was first introduced in 2001 and was quickly name the flagship vehicle of Aston Martin. It became extremely popular when it was featured as the official James Bond car in Die Another Day. The price tag of this car was $234,000, but it was discontinued in 2007 to make room for a newer model.


Source by: Phoenix Delray

Samsung Focus Windows Phone 7 Phone Review

Samsung Focus phone, with state-of-art Windows Phone 7 OS, a huge 4″ Super-AMOLED display and photo enhanced function for better viewing, and ultrathin body for grasping. Now let’s see Samsung Focus Windows Phone 7 Phone for more details.

1. Samsung Focus Windows Phone 7 phone—Body & Design

Samsung Focus cell phone is light and slim, with the dimension of 123 x 65 x 10 mm and weight of 115g, because of its plastic material. The streamlined body with ultrathin 9.9 mm thickness makes Samsung Focus glossy, elegant and grasp-friendly.

(1) Samsung Focus Cell Phone—Front

Samsung Focus cell phone offers 3 virtual keys (Return, Menu and Search) underneath a 4-inch huge touchscreen. The logos of “Samsung” and “AT&T” on the face, as well as “Windows Phone” on the rear indicate its identity—Samsung Focus is a cell phone with windows Phone 7 OS and is co-developed by Samsung and AT&T.

a. Samsung Focus—Screen

The selling point of Samsung Focus cell phone is its vivid Super-AMOLED capacitive touchscreen with 480x 800 high resolutions, which is ever applied to Samsung Galaxy series, bringing vivid viewing experience. Even in the open air, the image of screen is still vibrant.

b. Samsung Focus—Interface

The innovative interface of Windows Phone 7 OS breaks the stereotype, offering users different experience. Thanks to the WP7 OS, all the operation on Samsung Focus cell phone is smooth. It is worth mentioning that the screen switching and the speed of power on/off are faster and steadier than other phones. Samsung “Focus” focuses on every details, even the Samsung Hub and lock screen interface is also more authentic than that of HTC surround.

(2) Samsung Focus Cell Phone—Rear

Samsung Focus cell phone is glossy with engineering plastic material and the drawing processing in the rear, which greatly improves its quality. Distinguished V-lines in the rear of Samsung Focus makes it seem to have a third dimension.

In addition, you will also notice an AF 5MP camera with LED flashlight and a loudspeaker on the rear side. After removing the rear cover, you will find SIM and microSD card slots, together with a 1500 mAh battery like Samsung Galaxy S. Please don’t remove the Micro SD card when it is in use, otherwise Samsung Focus will restore to factory reset. If you insert it again, everything will return to normal.

(3) Samsung Focus Cell Phone—Keys and Ports

Top: a 3.5mm headset jack and microUSB port

Right: The power key of Focus is present on the right, which is not the same as most others that are found on the top side. You will also find a shutter key on the side.

Left: a volume rocker with chrome accented trim

2. Samsung Focus Windows Phone 7 phone—Configuration

Samsung Focus Windows Phone 7 phone comes with 1GHz Snapdragon QSD 8250 processor, but the 256MB of RAM seems to be slightly smaller than other Windows Phone 7 phones (512MB). But according to the news, Samsung confirmed they will offer 512MB RAM in November.

In addition, Samsung Focus cell phone also supports a microSD expansion slot for up to 40GB memory, including 4GB internal). When it comes to connectivity, Samsung Focus supports a 3.5mm audio jack, Bluetooth 2.1, WiFi 802.11b/g/n, microUSB 2.0, A-GPS and more.

(1) Samsung Focus Cell Phone—Camera

Samsung Focus windows phone 7 phone is impressive in terms of color restoration and details, with an AF 5MP camera with LED flashlight, but you can’t half press the shutter key to focus. Similar to HDR in iPhone, Samsung Focus adopts the WDR (wide dynamic range) technology, bringing a good performance on capturing still life photos. However, we are a bit disappointed with its 720P video recording effect with Low saturation and frame rate.

(2) Samsung Focus Cell Phone—Battery

Some people are likely to be worried a 1500mAh battery of Samsung Focus can’t feed its electronic-guzzling functions, like those Sky Drive photo syncs. In the test, we find that Samsung Focus will keep on working for more than one day even on heavy days of calling, emailing, gaming and browsing. Focus will support about 2 days with moderate use. When it drops into 10%-15% of battery power, please remember to charge it ASAP.

(3) Samsung Focus Cell Phone—Speech Quality

Samsung Focus Windows phone 7 phone has a good speech quality in normal environment. Although it supports dynamic noise reduction chip, the performance is not satisfied in noise test. Besides, Samsung Focus has high volume with powerful loudspeaker, but it will cause volume distortion at the same time.

3. Samsung Focus Windows Phone 7 phone—Summary

Do you focus on this “Focus” phone? Samsung Focus Windows Phone 7 phone is your best bet, which left us a deep impression on its vibrant super-AMOLED display, innovative Windows Phone 7 OS, and smooth & steady performance. We really hope more functions, like Fast Application switchover, copy and paste, will be applied to Samsung Focus cell phone in the near future.

(1) Samsung Focus Cell Phone—Pos:

  • Fast, smooth and state-of-art Windows Phone 7 OS
  • Vibrant Super-AMOLED screen display
  • Ultrathin and light body
  • Expandable memory up to 40G (including 4GB internal)
  • Good battery endurance
  • Enhanced photo effect

(2) Samsung Focus Cell Phone—Cons:

  • Absence of key features, like Fast Application switchover, copy and paste function
  • Remove MicroSD will cause hard reset
  • Disappointed video recording effect

4. Samsung Focus Windows Phone 7 phone—Specification

  • Operating System: Windows Phone 7
  • Processor: 1GHz Snapdragon QSD 8250 processor
  • Network: GSM: 850/900/1800/1900 MHz, UMTS: 850/1900/2100 MHz
  • Data: EDGE/UMTS/HSDPA 7.2 Mbit/s/HSUPA 2.0 Mbit/
  • Dimension: 4.84 x 2.56 x 0.39 inches (123 x 65 x 10 mm)
  • Weight: 4.07oz (115 g)
  • Display: 4-inch Capacitive, Multi-touch Super AMOLED screen display (480 x 800 pixels)
  • Camera: 5MP camera with LED Flash and 4 x digital zoom
  • Battery: 1500 mAh Li-ion, 6.5 hours (390 mins) of Talk time, 300 hours (12.5 days) of Stand-by time
  • Memory: 512RAM, 1GB ROM, expandable up to 40GB microSD (including 8GB internal)
  • Sensor: proximity sensor, light sensor, G-sensor
  • PhoneBook: Caller groups, multiple numbers per contact, Search by both first and last name, Picture ID, Ring ID
  • Connectivity: Bluetooth 2.1, WiFi 802.11b/g/n, 3.5mm audio jack, microUSB 2.0, HTML Browser, GPS, Outlook Sync Capability
  • Multimedia: FM Radio

Music Player: MP3, AAC, AAC+, eAAC+, WMA, WAV, AMR

Video Playback: MPEG4, H.263, H.264, WMV

  • Other Features :Alarms, Calendar, To-Do / Tasks, Document Viewer, Calculator, World Clock, Email, SMS


Source by: Cherry

Top 5 Smartphone development of 2009

As smartphones further paved their place in the enterprises, Apple, RIM Blackberry, Sony Ericsson, Nokia, Motorola and Google Android are eying for the spotlight. In the last quarter, Gartner said that Smartphone sales had surpassed 41 million units, a 12.8 percent increase compared to the same period last year.

Today, Smartphones have become a compulsory gadget for corporate users. They are not only revolutionizing the mobile handset market, but also changing the way we use PCs. The reason behind the success of the Smartphones is increased interest in social networking with Facebook and Twitter, which demand high speed internet and connectivity features.

In 2009, all the major mobile vendors update its range to increase their revenue and market share. Here, the feature discusses the biggest stories in the Smartphone industry.

1.    Google Android platform and Google Phone

Google Android is an open source mobile operating system running on the Linux kernel launched back in 2007. The platform targets mobile devices in large, but now it seems that various PC vendors are working on Android based netbooks and tablets. Recently, it is reported that the Android OS claimed 27% share in the market, whereas iPhone OS reported 55% share in the Smartphone market in US for November month.

Various Smartphones based on the platform is already available in the market like HTC G1, HTC Droid Eris, Motorola Droid, Samsung Galaxy, GW620 Eve, etc. Meanwhile, Google has been working on Android based Smartphone, called “Nexus One”, which will be available in January and will pose challenge Apple’s iPhone and RIM’s Blackberry.

2.    Apple updates its iPhone

In June, Apple launched the iPhone 3GS, with a boosted processor, better camera, more storage space, and a digital compass. The new Smartphone is more evolutionary up gradation than the revolutionary improvement to the hardware. The new iPhone 3GS has a number of new features which will certainly impress the corporate world like hardware encryption and support for ActiveSync policies. The new device fixed various anomalies of its predecessors and incorporated features like copy and paste, universal search, voice memos, and remote wiping.

3. Microsoft Windows mobile 6.5 OS

Microsoft launched a minor upgrade of its Windows Mobile 6.1 operating system in October for next generation of Smartphones, called Windows Mobile 6.5. The new software features a new UI and a richer browsing experience having new services like My Phone, which allows to synchronization of text messages, photos, video, contacts and more to the Web; and Windows Marketplace for Mobile.

Meanwhile, the company has been working on its new platform called Windows Mobile 7, codenamed “Photon”, which is a major upgrade planned for release in June 2010.

4. PC vendors join the Smartphone race

After the recent success of Smartphones and the take part in the pie, major PC vendors like Dell, Acer, HP, etc join the race with their handsets. In November, HP had announced its new iPAQ Glisten, a feature-rich 3G world Smartphone that meets the increasing demands of modern mobile professionals. In the same month, Dell Computers launched its Android-based Dell Mini 3 smartphone. Acer had introduced neoTouch, which is a new addition to its growing line of Windows Mobile 6.5 handsets, based on 1 GHz Snapdragon CPU.

5. Mobile App Market

According to latest research, mobile applications market will reach $9 billion by 2011. Apple has dominated the space with over 2 billion download and therefore other vendors are also entering in the field. However, the new apps will pose increased difficulty for developers.


Source by: Deepak

CURRENT CONCEPT IN DIAGNOSIS & MANAGEMENT OF GLAUCOMA

( Published by Cipla India to be distributed to Indian Ophthalmologists)

     Dr. M. R. Jain, a leading glaucoma specialist, is presently Medical Director and Chief Ophthalmologist M. R. J Institute and Jain Eye Hospital Jaipur, India. He has edited Text book on Glaucoma and a Book on OCULAR INFLAMMATION and published 130 scientific papers in India and abroad. In year 2007, he published public education book in Hindi on, ” EYES: SAFETY & TREATMENT”

He has been awarded LIFE TIME ACHIEVEMENT AWARD by Rajasthan Ophthalmological Society in the year 2002 & LIFE TIME ACHIEVEMENT AWARD by All India Ophthalmological Society, 2006

Dr. Jain is awarded Gold Medal by the ‘National Academy of Medical Sciences’ for research and clinical work in the field of “Glaucoma and Drug Delivery to the eye.”

Presently Dr Jain is Chairman, Dr M. R. J Charitable Trust, Chairman, Lucky Seventh, SMS Medicos and State Convener for National Academy of Medical Sciences.

 CURRENT CONCEPTS IN DIAGNOSIS AND

MANAGEMENT OF GLAUCOMA

PROF. M. R.JAIN, M.S., F.I.C.S.(USA), FAMS, FACLP( London) MEDICAL DIRECTOR M.R.J.INSTITUTE

& JAIN EYE HOSPITAL JAIPUR

E MAIL : drmrjain55@gmail.com

  

There has been a revolutionary change in understanding, diagnosis and management of glaucoma. Earlier the glaucoma was defined as a condition of raised intraocular pressure, not compatible with health and function of eye. Presently, American Academy Of Ophthalmology has defined glaucoma as an optic neuropathy with characteristic structural damage to optic nerve, associated with progressive retinal ganglion cell death, loss of nerve fibers and visual field loss. The importance of intraocular pressure above 21.0 mm of Hg as a singular factor has been significantly minimized since about one-third of patients might show classical glaucomatous damage with normal intraocular pressure (1,2) or in spite of controlled IOP after glaucoma surgery, there may be progressive loss of fields.

The definition of glaucoma is based on visually significant end-organ damage (3) . It is conclusively opined that IOP related damage can occur at all levels of IOP, and hence almost 50 percent of glaucoma patients remain undiagnosed (4-6) . However, Baltimore Eye Survey and Aravind Comprehensive Eye Study reveal that the relationship between the intraocular pressure and the prevalence of glaucoma is positive. Generally, 21mm of Hg is considered as a cutoff point.

  Top

 MODERN DIAGNOSTIC MODALITIES

  

OPTIC NERVE HEAD IMMAGING

In addition to the well established Direct Ophthalmoscopy and Slit Lamp Indirect Ophthalmoscopy using 90 diopters of lens, newer diagnostic tools are available to precisely visualize and document subtle changes in the disc, depending upon the contour, colour, cupping and the health of neuroretinal rim. (7-10) These are as follows:

1. PHOTOGRAPHY TECHNIQUE

(a) STEREO PHOTOGRAPHS

2. COMPUTERISED IMAGE ANALYSIS

(a) OPTICAL COHERENCE TOMOGRAPHY (OCT)

(b) CONFOCAL SCANNING LASER TOMOGRAPHY (CSLT)

(c) SCANNING LASER POLARIMETRY (SLP).

These modalities are especially useful to quantitatively assess retinal nerve fibre layer (RNFL) thickness in addition to changes in the disc in suspected cases of glaucoma. It is established that retinal nerve fibre layer in glaucoma may show thinning even before the field changes are detected (11-14).

Optical Coherence Tomography (OCT) scan of a normal 2 glaucomatous eye, showing nerve fibre thickness.

Heidelberg Retinal Tomograph (HRT and HRT II) is a confocal laser scanning system for acquisition and analysis of three-dimensional images of optic nerve head. HRT imaging system has the highest diagnostic precision, accuracy, reproducibility and is able to diagnose glaucoma before confirmed visual field change. (15,16)

Kamal et al (17) and Greaney et al (18) observed that imaging techniques were not better than quantitative assessment of disc photographs. In addition to progressive excavation of the optic disc, the health of neuroretinal rim evidenced by its width and colour is very important (8) . Localized unilateral notch in the inferio-temporal or superio-temporal part of neuroretinal rim is strong indicator of glaucoma. Several other soft signs like asymmetry of cup/disc ratio greater than 0.2, peripapillary halo, disc hemorrhage, Herschler’s sign of exposed floor vessels, vertical ovality of optic cup with a ratio of greater than 3 and few others when present, adds to suspicion of glaucoma. In recent years, more importance is given to a disc hemorrhage crossing the rim of the optic nerve and it is considered to be associated with the acquired pit of the optic nerve (APON), which is a very strong association of glaucoma (16,19) .

  Top

 ADVANCEMENT IN AUTOMATED FIELD RECORDING

  

Introduction of computerized automated field testing has helped us significantly to diagnose glaucoma at an early stage as well as it provides certain amount of documentation to monitor the control and progression of glaucoma.

Last decade has seen immense advances in test strategies, which has made the process quick, precise, reliable and reproducible. (20,21)

SITA (Swedish Interactive Threshold Algorithm) and TOP (Tendency Oriented Perimetry) test strategies have reduced the testing time and provided variability of automated perimetric testing.

Frequency Doubling Technology (FDT) perimetry is very rapid and effective method to detect glaucomatous field loss.

Short Wavelength Automated Perimetry (SWAP) is able to predict the onset and progression of glaucomatous visual field deficits much earlier than the Standard Automated Perimetry (SAP)

Multifocal Electroretinogram (mfERG) and Multifocal Visual Evoked Potential (mfVEP) provide an objective measurement of the visual field.

Recent studies suggest that mfVEP procedures may be able to detect glaucomatous damage earlier than the conventional automated perimetry. Goldberg and associates (22) noted that 60 percent of fellow eyes of glaucoma patients that had normal Humphrey visual field were identified as abnormal by the mfVEP.

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 INTRAOCULAR PRESSURE

  

Last decade has not seen any significant advancement in the methodology of recording IOP. In spite of several types of tonometers including Applanation Pneumatonograph, Mackay Marg Electronic Tonometer, (23-27) , Tonopen XL (blood flow tonometer) (28) and even Non Contact Tonometer, Goldman Tonometer remains the most reliable clinical Tonometer, wherever it is possible to employ this technique. Non Contact Tonometer is convenient to the patient and to the doctor but the readings quite often does not compare well with the Goldman Tonometer. The machine needs repeated standardization and has several limitations. Apart from scleral rigidity, abnormal central thickness of the cornea can affect the intraocular pressure reading (29, 30) .

What has changed in the last decade is the understanding of ideal IOP. Such an IOP has been labelled as TARGET IOP.

Target IOP is defined as that IOP which is safe for that particular person. It may be anywhere between low-teens to 21 mmHg.

Target IOP is set on following principles :

a. Mild Field Loss: Reduce IOP 20% less of initial IOP

b. Moderate Damage: 30% reduction or more.

c. Severe Damage: 40% reduction or more.

There is no IOP at which an individual is completely safe from glaucoma damage and hence target IOP has to be individualized depending upon repeated examination of disc and the fields. Risk factors such as aging, myopia, heredity, diabetes etc (31) too have to be kept in mind.

The outcome of the Advanced Glaucoma Intervention Study (AGIS) data suggest that lower the IOP the better, regardless of other risk factors that are accounted for clinically. In younger patients, the IOP should be maintained relatively low (32) .

Most therapeutic decisions in glaucoma are based on the steady state pressure. Ophthalmologists rarely document transient or episodic spikes in pressure or consider the damage that such spikes can cause. But such episodic spikes are significantly damaging to the RGS (33) . Postural change in IOP where the IOP is reported to increase in supine posture as compared to sitting posture, which is usually employed in Goldmann or Non- Contact Tonometry, may miss some of the glaucoma cases (23-27).

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 PERFUSION PRESSURE

   

Glaucomatous field damage is associated with decrease in perfusion pressure of lamina cribrosa and neuroretinal rim. It is opined that vascular deregulation interferes with the auto regulation of ocular perfusion and renders the eye more sensitive to IOP increase or blood pressure decrease. This partly explains the theory of field loss at low intraocular pressure and highlights the significance of using only those anti-glaucoma drugs, which do not compromise the perfusion pressure of the optic disc (34,35).

Perfusion pressure of the disc can be measured precisely by following techniques:

Heidelberg Retinal Flometer

OBF Tonograph

Scanning Laser Doppler Flometry

Colour Doppler Measurements

Some workers have stated that lack of proper perfusion of optic disc is the main cause of field loss. Such a decrease in perfusion pressure may be due to raised IOP or may be pressure independent, which explains the occurrence of Low Tension Glaucoma (36-40) . Some patients with normal tension glaucoma are particularly at risk if they have history of vasospasm and migraine headache and that accounts for the use of calcium channel blockers to prevent glaucomatous damage. It is note worthy that the perfusion pressure of the optic disc can recover with the lowering of IOP, especially after a successful trabeculectomy (41).

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 APOPTOSIS (PROGRAMMED CELL DEATH)

  

A normal person loses almost 10,000 ganglion cells per year, and by the time they are 80 years of age, they will have lost 30 percent of their ganglion cells. In the case of open angle glaucoma, by the time vision loss becomes apparent, more than 50 percent of ganglion cells are destroyed.

                                                     

Apoptosis is a genetically programmed process in which cells commit suicide, characterized by chromatic condensation, intracellular fragmentation, and internucleosomal DNA fragmentation. (42-44)

Retinal ganglion cell death is initiated when some pathological event, such as ischemia, axonal injury, or changes in the lamina cribrosa leads to activation of apoptosis (programmed cell death).

Apoptosis may occur due to primary or secondary mechanisms.

Primary Mechanisms are:

Mechanical Stress : Raised IOP can interfere with retrograde axoplasmic flow of essential growth factors produced by the lateral geniculate nucleus.

Vascular Compromise : Elevated IOP, vascular disease or drugs can reduce perfusion of optic nerve, causing ischemic conditions.

Genetic Determinants : Genetic determinants may also contribute to the ganglion cells susceptibility to damage (45)

Diseases like diabetes may also make neurons more vulnerable to damage.

Secondary Mechanisms:

In this the neuronal damage is believed to be driven by toxic factors, such as high levels of glutamate (in normal levels it is a neurotransmitter), oxygen free radicals, or nitric oxide, which can be released by a primary insult, leading to continued damage, even after the primary insult has been controlled or dissipated.

Glutamate, an amino acid when in excess becomes toxic to the neuronal cells, thereby initiating the process of apoptosis. Dead cells are thought to liberate glutamate and other amino acids, which keep on the vicious circle of “Programmed Death of Ganglion Cells”. It is now known that glutamate is a normal neurotransmitter in the retina which when accumulates in excess probably as a result of dead or dying cells, cause further damage to living cells.

Oxygen Free Radicals (OFR) are oxygen-containing molecules that carry one or more unpaired electrons. These molecules react with lipids, nucleic acids, and proteins and cause cell death. Ischemia which may be pressure independent, is supposed to help in the process of liberation of OFR.

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 NEUROPROTECTION (ENHANCING CELL SURVIVAL)

  

The term “neuroprotection” refers to the protection of healthy but vulnerable neurons in the vicinity of dead and dying cells, which are at risk of injury even after the removal of the primary insult. In glaucoma, the goal of neuroprotection is to limit or retard pressure-dependent or pressure-independent damage to retinal ganglion cells (RGCs) by interfering with the processes and substances that cause neuronal cell death or by enhancing signaling pathways that increase neuronal survival under stressful conditions. (42,43, 45-47)

Researchers are trying to find the intrinsic processes or natural pathways to interrupt the process of apoptosis and promote survival of ganglion cells by inhibiting death signals released in the presence of ischemia, elicited by the deprivation of growth factors, or caused by over accumulation of excitatory amino acids such as glutamate (48) .

Glutamate quantity is demonstrated to increase to double in the vitreous in cases of glaucoma.

Neuroprotection is based on the principal of

Reduce risk factors: Lower the IOP, reduce ischemia.

Promote neuronal survival

And/or inhibit cell death

Excess glutamate can be toxic to normal RGSs through over stimulation of N-Methyl-D-Asparate (NMDA) receptors. The NMDA receptor is a major type of glutamate receptor that when over activated can kill retinal ganglion cells. Memantine, derived from amantidine, shows considerable promise for neuroprotective efficacy in glaucoma. Memantine’s non-competitive interaction with the NMDA receptor results in blockade of the toxic effects of glutamate without significant effect on normal cellular function. The greater the NMDA receptor activation by glutamate, the more effectively memantine blocks the action of glutamate, thereby preventing ganglion cell death. (49)

The Bcl-2 family of gene proteins performs a central role in regulating apoptosis. Members of Bcl-2 gene family that promote programmed cell death include bad and bax; in contrast, the expression of bcl-2 and bcl-xl suppresses the apoptic programme. To date, a -2 pathways have been identified that increase expression of bFGF, induce bcl-2 and bcl-xl genes, and enhance the availability of important neurotrophic factors. By activating the alpha-2 receptors in the retina, Brimonidine (Brimodin) is demonstrated to increase anti-apoptic gene expression, thereby, preventing retinal ganglion cell death and promoting axonal growth (50) . Brimonidine also neutralizes Kainic acid, which is toxic to neuronal cells.

Antioxidants, free radical scavenger superoxide dismutase, catalase and vitamin E are also found to have potential neuroprotective utility.

Calcium channel blockers (diltiazem, nicardipin, nilvadipine, nifedipine etc), semax (Russian neuropeptide), citicoline, eliprodil, riluzole and L-deprenal etc are under study as neuroprotective agents.

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 MEDICAL THERAPY

  

With numerous existing drugs and new classes of medications now available for lowering IOP, practitioners are facing complex decisions regarding treatment strategies for glaucoma patients. Traditionally, beta-blockers have been considered the standard treatment for glaucoma, but other agents, such as a -2 agonists, carbonic anhydrase inhibitors and prostaglandins have offered alternative options to the clinician. More recently, a new group, namely, Prostamide group has come on the scene with claims of improved safety, efficacy and dosing regimen compliance by the patient, compared to previously available agents.

In general, anti-glaucoma drugs are chosen based on following criteria :

Efficacy is most vital

Systemic safety profiles

The convenience of treatment- preferred OD therapy

The cost of therapy

Local tolerances

Depending on above referred criteria, beta-blockers, especially the Timolol, which is the most efficacious agent out of the group, has dominated the anti-glaucoma regimen. The drug is considered quite efficacious, reducing IOP by 15 to 30 percent, relatively inexpensive and with excellent toleration by ocular tissue makes them still the highly recommended primary therapy of glaucoma in the world. (What warrant is adverse systemic effects on respiratory and cardiovascular system, and the issues such as depression, impotence, lack of libido, diabetes and nocturnal hypo tension (51,52) ). Lack of vigilance on the part of physician can cause death of the patient due to status asthmaticus or cardiovascular complication. Since the introduction of the drug in 1978, 40 drug-induced deaths have been reported. Systemic toxicity can be significantly minimized if the clinician is cautious in advising the use of this drug and takes measures to prevent systemic absorption by using precise dispensers, pressure on the lower puncta or using once a day gel-forming (Timolet GFS) application. Selective beta-blockers like Betaxolol, is relatively safe in patients with respiratory problems but is less efficacious than timolol.

Pilocarpine still continues to occupy its importance in Primary Angle Closure Glaucoma. The drug has synergistic effect with beta-blockers, brimonidine and systemic and topical acetazolamide group of drugs.

Adrenergic agents (agonists) like dipivefrin, clonidine and apraclonidine have limited specific indications since quite often they are associated with conjunctival allergy and other side effects including decrease in perfusion pressure of the optic disc.

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 NEWER DRUGS

  

Brimonidine tartrate 0.2%

Latanoprost 0.005%

Bimatoprost 0.03%

Travoprost 0.004%

Unoprostone Isopropyl 0.12%

Dorzolamide 2%

Brinzolamide 1% (Azopt)

Brimonidine Tartrate:

Brimonidine is a-2 selective agonist. It is an analogue of clonidine. It is about 30 fold more a -2 selective and has very low affinity for a -1 receptors. Due to this reason, mydriasis and lid lag as found with non-selective agonists like clonidine are eliminated.

Its main mechanism of action is suppression of aqueous formation, but it is also claimed to increase some degree of uveoscleral out – flow.

(The most significant merit of brimodine (Brimodin) is its relative systemic safety profile and its postulated function of neuroprotection through upregulation of cellular and neuronal survival factors, such as bFGF1 in response to activation of the a -2 adrenergic receptors, and increase in ocular blood flow. (53-55)) The drug has to be instilled twice a day and its IOP lowering effect can be compared to timolol. The demerit is higher IOP at trough. The limiting factor of brimonidine is its allergic reactions in the form of contact dermatoconjunctivis and follicular conjunctivitis (approximately 30 percent eyes), which may warrant discontinuation of the drug. In recent years, few reports have shown occurrence of uveitis after prolonged use of brimonidine tartrate. Other occasional side effects reported are fatigue, drowsiness and dryness of mouth. The newer introduction of preservative free brimonidine is reported to have much less allergy (50% reduction) since instead of benzalkonium chloride, sodium chloride has been used as a preservative. Therapeutically, it is equally effective as briomonidine.

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 Prostaglandin Analogues and Prostamides

  

Prostaglandins and prostamides are newer group of drugs. Inspite of their heavy cost, they are gaining great importance due to their higher efficacy in reduction of IOP, require single instillation in 24 hours, and have relatively safe systemic profile (56-62)

Prostaglandin and prostamide have a common origin within cell membranes but they are derived from different membrane-bound lipids that are mobilized and undergo biosynthetic pathways to their final compounds. The prostaglandin F2 alpha analogues are derived from an arachidonic acid intermediary in their metabolism and formation, but the prostamides are derived from an anandamide pathway where different enzymes are involved. Although prostamides are structurally similar in some respects to prostaglandins, functionally prostamides differ.

Latanoprost, travoprost & bimatoprost are reported to decrease IOP by 30 to 40 percent and hence they can be the drug of choice as monotherapy in eyes requiring lower target IOP. Superior diurnal control (24-hour control) achieved with these drugs, prevents spikes related damage to the eyes (56) . A comparison of bimatoprost to timolol showed that a statistically significant number of patients using bimatoprost achieved given target IOP at each time point compared to those using timolol. (63) Latamoprost too achieved target IOP but bimatoprost often achieved lower IOP.

Prostaglandin analogues increase uveoscleral outflow without affecting trabecular outflow or the production of aqueous humour. The increased uveoscleral outflow appears to be mediated via a modification of the extracellular matrix and a relaxation of ciliary muscle.

Latanoprost too is essentially an outflow-enhancing drug. There is 50% increase in uveoscleral outflow (64-68) and 30% increase in trabecular outflow through a mechanism, which is yet to be explained. There is slight enhancement of inflow also. (69) Latanoprost is reported to increase blood flow to optic nerve head. (67, 68)

Recent comparative studies show Lataoprost to be more effective than unoprostone and Timolol but less than brimatoprost.(56) Bimatoprost lowered IOP by 30% in approximately 78% of patients, while timolol achieved 30% reduction in only 61% of patients. (56) Furthermore, 62% of patients receiving Bimatoprost got 40% reduction in IOP compared to 35% of patients receiving Timolol. The combination of Latanoprost with timolol when used once a day give better IOP lowering than latanoprost alone. (69) Few workers (70,71) noted additional decrease in IOP when pilocarpine was used four times a day along with single application of Latanoprost.

The greatest drawback of prostaglandins and prostamides is significant ocular side effects manifested in the form of conjunctival hyperemia (15%), stinging and burning (30-40%) and foreign body sensations (20-22%), growth of eye lashes, increased pigmentation of iris and periorbital tissue including eyelids, cystoid macular edema, herpes simplex keratitis, and uveitis.

These drugs are reported to lose efficacy by 10 to 20% if exposed to ultraviolet rays unless kept in opaque bottles brimatoprost or in refrigerator latanoprost.

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 CARBONIC ANHYDRASE INHIBITORS (CAIs)

  

Topical CAIs have been developed that have much improved systemic side effect profile when compared with their oral counterparts. However, the topical CAIs are less efficacious than the oral agents. Dorzolamide and brinzolamide reduce IOP by approximately 15 to 24% and are not effective in all patients.

Significant ocular side effects like burning, stinging, foreign body sensation, superficial punctuate keratitis etc are noted. In addition, in some cases, sulpha like systemic effects may be noted. Due to these reasons these drugs are mostly employed as second or third-line therapy.

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 ADJUNCTIVE THERAPY

  

Brimonidine (Brimodin) is as effective as pilocarpine when used adjunctively with beta-blockers, decreasing the IOP almost 15% more. Dorzolamide when added to timolol does not significantly affect IOP. Prostaglandins and Prostamides can be used as second-line of therapy along with beta blockers, (69) brimonidine (Brimodin), clonidine and CAI agents. Pilocarpine when used four times a day along with latanoprost, gives additional IOP lowering. (71) Prostamides cause relaxation of ciliary muscle and hence pilocarpine is reported to be additive

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 SUMMARY

  

Much progress has been made in the diagnosis and management of glaucoma but still certain number of cases can only be labeled as suspicious and the medical management still remains challenging.

Cholinergic agents and non-selective a -adrenergic receptor antagonists have been replaced for the most part by newer agents that are better tolerated and have fewer ocular and systemic side effects. Although the beta-adrenergic receptor antagonists are very effective IOP-lowering agents that have been the standard line of treatment for last 20 years but their serious cardio-pulmonary side effects restricts their use. Concept of apoptosis, perfusion pressure of the optic disc, neuroprotection, metabolic toxins, autoimmune process and genetic mutation has added new dimensions to the medical management of glaucoma. brimonidine (Brimodin), an a -2 adrenergic receptor agonist, has good IOP lowering effect and systemic safety profile and is postulated to have the property of neuroprotection but ocular reactions are still a challenge. Treatment with CAI agents like dorzolamide and brinzolamide cannot be considered first line therapy and are effective only in some. Systemic and ocular side effects limit their use.

Prostaglandins and prostamides are promising drugs due to their enhanced IOP lowering effect, once a day application and high systemic safety profile. However, their ocular side effects are a serious matter of concern, especially in white population.

We are still in search of an ideal drug with safe profile, significant IOP lowering and proved neuroprotection without compromising perfusion pressure of the optic disc. Memantine could probably be the drug of tomorrow to be used with other ocular hypotensive drugs as a ‘cocktail’ to achieve the desired results.

A new glaucoma management paradigm has emerged; whereby clinical success is no longer simply measured by the level of intraocular pressure control achieved but also by patient’s quality of life, cost effectiveness of therapy, and the long-term preservation of visual function.

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Source by: DR M. R. JAIN

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